Overcoming Therapeutic Resistance of Bone Sarcomas: Overview of the Molecular Mechanisms and Therapeutic Targets for Bone Sarcoma Stem Cells

Table 2

Regulators of bone sarcoma stem cells.

Subtype	Category	Regulators	Target CSC	Function, clinical relevance	Reference
Osteosarcoma	Signaling pathways	MAPK	3AB-OS	Self-renewal, tumorigenicity	[60, 61]
		Wnt/β-catenin	Sarcosphere, SP	Tumorigenicity, drug resistance, invasion	[64, 65]
		Notch	ALDH	Oxidative stress, migration, invasion, VEGF expression	[69]
		TGF-β	Sarcosphere	Dedifferentiation, clonogenicity	[70]
		TNF-α	AX	Tumorigenesis, differentiation	[71]
		BMP2	ALDH	Tumorigenesis, stem-cell marker, differentiation marker	[72]
Osteosarcoma	Epigenetic regulators	miR-29b	3AB-OS	Sphere, clonogenicity, drug resistance	[76]
		miR-133a	CD133	Invasion, metastasis, prognosis	[77]
		miR-143	CD133/ALDH	Drug resistance, autophagy, prognosis	[78]
		miR-1247	CD117/Stro-1	Sphere, proliferation	[79]
		HIF2PUT	CD133	Sphere, proliferation, migration, alteration of HIF2-α mRNA	[82]
		Telomerase	Sarcosphere	Sphere, invasion, drug resistance, tumorigenicity	[85]
		TSSC3	Sarcosphere	Sphere, clonogenicity, apoptosis, regulate Oct3/4, Nanog, and Sox2	[86]
		MLH1, MSH2	Sarcosphere	Drug resistance	[19]
Ewing sarcoma	Epigenetic regulators	TARBP2	CD133	Tumorigenicity, CD13 frequency	[81]
		miR-145	CD133	Tumorigenicity	[80]
		miR-143, -145	CD133	Clonogenicity, tumorigenicity	[81]